Methods for selecting medications for treating patients having attention-deficit hyperactivity disorder

A method of selecting a medication and treating a patient having ADHD, the method comprising:

• (a) genotyping a biological sample from a patient to determine the patient's genotype for a set of markers of a panel of genes using a method comprising one or more of a polymerase chain reaction (PCR) based nucleic acid amplification step, allele specific hybridization, and allele specific restriction digests, and the set of markers and genes comprising the following:
• (i) one or more cytochrome P450 CYP2D6 alleles selected from the group consisting of *2BD, *3, *4, *5, *6, *7, *8, *9, *10, *11, *12, *15, *17, and *41;
• (ii) the tandem duplication polymorphism in the promoter region of the dopamine receptor DRD4 gene that consists of a 120 base pair allele and a 240 base pair allele;
• (iii) the G1278A polymorphism in exon 9 of the norepinephrine transporter gene SLC6A2;
• (iv) the 10 repeat unit and the 9 repeat unit of the variable number tandem repeat (VNTR) polymorphism in the dopamine transporter gene SLC6A3;
• and
• (v) the G158A polymorphism in the catechol-O-methyl transferase gene COMT;
• (b) receiving, in a computer system, the patient's genotype determined in (a) and assigning a phenotype for each gene based on the patient's genotype as follows:
• a CYP2D6 phenotype selected from phenotype 1, phenotype 2 and phenotype 3, wherein a homozygous or compound heterozygous genotype for any of the alleles in (i) is assigned phenotype 1, a heterozygous genotype for any of the alleles in (i) is assigned phenotype 2, and a genotype lacking any of the alleles in (i) is assigned phenotype 3;
• a DRD4 phenotype selected from a positive phenotype if the genotype is homozygous for the rare 120 allele and a negative phenotype if the common 240 allele is present;
• a SLC6A3 phenotype selected from a positive phenotype if the genotype is homozygous for the 10 repeat unit and a negative phenotype if the 9 repeat unit is present;
• a SLC6A2 phenotype selected from a positive phenotype if the genotype is G/A or G/G and a negative phenotype if the genotype is A/A;
• a COMT phenotype selected from an active phenotype if the genotype is val/val and a less active phenotype if the genotype is val/met or met/met;
• (c) combining, using said computer system, each assigned phenotype for each gene of the panel of genes into a combined phenotype for the patient;
• (d) applying a set of rules to select a medication for the patient based upon the patient's combined phenotype;
• (e) outputting the selection of medication according to the patient's combined phenotype as follows:
• the patient has a combined phenotype selected from:
• (i) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT active phenotype;
• CYP2D6 phenotype 2;
• (ii) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT active phenotype;
• CYP2D6 phenotype 3;
• (iii) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 positive phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 2;
• (iv) DRD4 negative phenotype;
• SLC6A3 positive phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 2;
• (v) DRD4 positive phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 2;
• (vi) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 2;
• (vii) DRD4 negative phenotype;
• SLC6A3 positive phenotype;
• SLC6A2 positive phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• (viii) DRD4 positive phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 positive phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• (ix) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 positive phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• (x) DRD4 positive phenotype;
• SLC6A3 positive phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• (xi) DRD4 negative phenotype;
• SLC6A3 positive phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• (xii) DRD4 positive phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• and
• (xiii) DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 3;
• and the output is amphetamines or atomoxetine;
• or
• the patient has a combined phenotype that is:
• DRD4 negative phenotype;
• SLC6A3 negative phenotype;
• SLC6A2 negative phenotype;
• COMT less active phenotype;
• CYP2D6 phenotype 1;
• and the output is low dose atomoxetine;
• and
• (f) administering to the patient a medication selected from amphetamines, atomoxetine, or low dose atomoxetine according to the output for the patient's combined phenotype in step (e),
• thereby treating the ADHD in the patient.